| Outcome |
Relative effect 95%CI |
LoD |
Trt. better when |
|
I2 |
k (RCT/OBS)
|
Bayesian probability
|
Overall ROB
|
Publication bias |
Degree of certainty |
Endpoint importance |
Published MA |
efficacy endpoints 00 |
| deaths (OS) | 0.86 [0.80, 0.92] | | < 1 | | 27% | 10 studies (10/-) | 100.0 % | some concern | low | moderate | crucial | - |
| deaths (OS) (extension) | 0.77 [0.70, 0.85] | | < 1 | | 0% | 3 studies (3/-) | 100.0 % | some concern | not evaluable | moderate | important | - |
| PFS (extension) | 0.72 [0.41, 1.26] | | < 1 | | 95% | 2 studies (2/-) | 87.4 % | some concern | not evaluable | moderate | important | - |
| progression or deaths (PFS) | 0.90 [0.74, 1.09] | | < 1 | | 84% | 8 studies (8/-) | 85.9 % | some concern | not evaluable | moderate | important | - |
| RFS/DFS | 0.72 [0.59, 0.88] | | < 1 | | 0% | 1 study (1/-) | 99.9 % | NA | not evaluable | | important | - |
| CRR | 1.96 [1.21, 3.17] | | > 1 | | 0% | 1 study (1/-) | 99.7 % | NA | not evaluable | | non important | - |
| DCR | 1.85 [1.35, 2.54] | | > 1 | | 0% | 1 study (1/-) | 100.0 % | NA | not evaluable | | non important | - |
| DMFS | 0.75 [0.59, 0.95] | | < 1 | | 0% | 1 study (1/-) | 99.2 % | NA | not evaluable | | non important | - |
| DOR | 0.49 [0.24, 1.00] | | < 1 | | 88% | 6 studies (6/-) | 97.5 % | some concern | not evaluable | moderate | non important | - |
| events or deaths (EFS) | 0.80 [0.63, 1.01] | | < 1 | | 57% | 2 studies (2/-) | 96.9 % | some concern | not evaluable | moderate | non important | - |
| objective responses (ORR) | 0.92 [0.59, 1.43] | | > 1 | | 93% | 9 studies (9/-) | 35.5 % | some concern | not evaluable | moderate | non important | - |
| objective responses (ORR) (extension) | 2.16 [1.34, 3.48] | | > 1 | | 0% | 1 study (1/-) | 99.9 % | NA | not evaluable | | non important | - |
safety endpoints 00 |
| AE (any grade) | 0.85 [0.13, 5.43] | | < 1 | | 94% | 5 studies (5/-) | 56.7 % | some concern | not evaluable | moderate | non important | - |
| AE (grade 3-4) | 0.64 [0.31, 1.33] | | < 1 | | 97% | 7 studies (7/-) | 88.4 % | some concern | not evaluable | moderate | non important | - |
| AE (grade 3-5) | 0.76 [0.19, 3.00] | | < 1 | | 96% | 2 studies (2/-) | 65.4 % | some concern | not evaluable | moderate | non important | - |
| AE leading to death (grade 5) | 1.80 [1.18, 2.75] | | < 1 | | 50% | 7 studies (7/-) | 0.3 % | some concern | not evaluable | moderate | non important | - |
| AE leading to treatment discontinuation (any grade) | 0.82 [0.46, 1.46] | | < 1 | | 93% | 9 studies (9/-) | 74.5 % | some concern | not evaluable | moderate | non important | - |
| AE leading to treatment discontinuation (grade 3-4) | 0.85 [0.44, 1.65] | | < 1 | | 0% | 1 study (1/-) | 68.1 % | NA | not evaluable | | non important | - |
| SAE (any grade) | 1.12 [0.89, 1.41] | | < 1 | | 72% | 6 studies (6/-) | 16.7 % | some concern | not evaluable | moderate | non important | - |
| STRAE (any grade) | 0.81 [0.51, 1.29] | | < 1 | | 90% | 8 studies (8/-) | 81.0 % | some concern | not evaluable | moderate | non important | - |
| TRAE (any grade) | 0.57 [0.18, 1.81] | | < 1 | | 98% | 9 studies (9/-) | 83.1 % | some concern | not evaluable | moderate | non important | - |
| TRAE (grade 3-4) | 0.37 [0.17, 0.81] | | < 1 | | 98% | 10 studies (10/-) | 99.3 % | some concern | low | moderate | non important | - |
| TRAE leading to death (grade 5) | 0.75 [0.39, 1.44] | | < 1 | | 38% | 9 studies (9/-) | 80.7 % | some concern | not evaluable | moderate | non important | - |
| TRAE leading to discontinuation (any grade) | 0.73 [0.30, 1.79] | | < 1 | | 89% | 5 studies (5/-) | 75.6 % | some concern | not evaluable | moderate | non important | - |
TRAE (grade 3-4) endpoints 00 |
| Abdominal pain TRAE (grade 3-4) | 2.15 [0.19, 24.47] | | < 1 | | 0% | 2 studies (2/-) | 27.1 % | some concern | not evaluable | moderate | non important | - |
| Acute kidney injury TRAE (grade 3-4) | 2.04 [0.41, 10.20] | | < 1 | | 0% | 3 studies (3/-) | 19.5 % | some concern | not evaluable | moderate | non important | - |
| Adrenal insufficiency TRAE (grade 3-4) | 1.89 [0.49, 7.28] | | < 1 | | 0% | 7 studies (7/-) | 17.9 % | some concern | serious | moderate | non important | - |
| Alopecia TRAE (grade 3-4) | 0.67 [0.09, 4.84] | | < 1 | | 0% | 3 studies (3/-) | 65.4 % | some concern | not evaluable | moderate | non important | - |
| Anaemia TRAE (grade 3-4) | 0.13 [0.05, 0.39] | | < 1 | | 93% | 8 studies (8/-) | 100.0 % | some concern | serious | moderate | non important | - |
| Arthralgia TRAE (grade 3-4) | 2.54 [0.36, 17.86] | | < 1 | | 0% | 3 studies (3/-) | 17.6 % | some concern | not evaluable | moderate | non important | - |
| Arthritis TRAE (grade 3-4) | 1.24 [0.14, 10.65] | | < 1 | | 0% | 3 studies (3/-) | 42.2 % | some concern | not evaluable | moderate | non important | - |
| Asthenia TRAE (grade 3-4) | 0.62 [0.35, 1.10] | | < 1 | | 40% | 10 studies (10/-) | 94.8 % | some concern | low | moderate | non important | - |
| Blood creatinine increased TRAE (grade 3-4) | 0.74 [0.10, 5.30] | | < 1 | | 0% | 3 studies (3/-) | 61.5 % | some concern | not evaluable | moderate | non important | - |
| Chills TRAE (grade 3-4) | 1.00 [0.02, 50.69] | | < 1 | | 0% | 1 study (1/-) | 49.9 % | NA | not evaluable | | non important | - |
| Colitis TRAE (grade 3-4) | 2.81 [1.08, 7.34] | | < 1 | | 0% | 7 studies (7/-) | 1.8 % | some concern | not evaluable | moderate | non important | - |
| Constipation TRAE (grade 3-4) | 0.29 [0.07, 1.23] | | < 1 | | 35% | 6 studies (6/-) | 95.3 % | some concern | not evaluable | moderate | non important | - |
| Decreased appetite TRAE (grade 3-4) | 0.77 [0.37, 1.60] | | < 1 | | 0% | 8 studies (8/-) | 75.7 % | some concern | not evaluable | moderate | non important | - |
| Dermatitis acneiform TRAE (grade 3-4) | 0.99 [0.02, 50.11] | | < 1 | | 0% | 1 study (1/-) | 50.2 % | NA | not evaluable | | non important | - |
| Diabetes TRAE (grade 3-4) | 1.47 [0.33, 6.48] | | < 1 | | 0% | 6 studies (6/-) | 30.5 % | some concern | serious | moderate | non important | - |
| Diarrhoea TRAE (grade 3-4) | 1.20 [0.68, 2.12] | | < 1 | | 0% | 7 studies (7/-) | 26.7 % | some concern | not evaluable | moderate | non important | - |
| Dry skin TRAE (grade 3-4) | 1.00 [0.02, 50.69] | | < 1 | | 0% | 1 study (1/-) | 49.9 % | NA | not evaluable | | non important | - |
| Dyspnoea TRAE (grade 3-4) | 2.15 [0.19, 24.47] | | < 1 | | 0% | 2 studies (2/-) | 27.1 % | some concern | not evaluable | moderate | non important | - |
| Eczema TRAE (grade 3-4) | 0.99 [0.02, 50.11] | | < 1 | | 0% | 1 study (1/-) | 50.2 % | NA | not evaluable | | non important | - |
| Endocrine disorders TRAE (grade 3-4) | 1.99 [0.07, 59.38] | | < 1 | | 0% | 1 study (1/-) | 34.8 % | NA | not evaluable | | non important | - |
| Erythema TRAE (grade 3-4) | 0.99 [0.02, 50.11] | | < 1 | | 0% | 1 study (1/-) | 50.2 % | NA | not evaluable | | non important | - |
| Fatigue TRAE (grade 3-4) | 0.60 [0.36, 1.00] | | < 1 | | 25% | 10 studies (10/-) | 97.5 % | some concern | low | moderate | non important | - |
| Febrile neutropenia TRAE (grade 3-4) | 0.10 [0.03, 0.39] | | < 1 | | 0% | 3 studies (3/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
| Gastritis TRAE (grade 3-4) | 1.36 [0.10, 17.75] | | < 1 | | 0% | 2 studies (2/-) | 40.8 % | some concern | not evaluable | moderate | non important | - |
| Gastrointestinal disorders TRAE (grade 3-4) | 2.00 [0.50, 8.06] | | < 1 | | 0% | 1 study (1/-) | 16.5 % | NA | not evaluable | | non important | - |
| Guillain-Barré syndrome TRAE (grade 3-4) | 1.57 [0.20, 12.15] | | < 1 | | 0% | 3 studies (3/-) | 33.5 % | some concern | not evaluable | moderate | non important | - |
| Hepatitis TRAE (grade 3-4) | 2.72 [0.53, 14.06] | | < 1 | | 0% | 4 studies (4/-) | 11.7 % | some concern | not evaluable | moderate | non important | - |
| Hypersensitivity TRAE (grade 3-4) | 0.46 [0.04, 5.04] | | < 1 | | 0% | 2 studies (2/-) | 73.7 % | some concern | not evaluable | moderate | non important | - |
| Hyperthyroidism TRAE (grade 3-4) | 1.14 [0.24, 5.40] | | < 1 | | 0% | 6 studies (6/-) | 43.7 % | some concern | serious | moderate | non important | - |
| Hypophysitis TRAE (grade 3-4) | 3.36 [0.66, 17.24] | | < 1 | | 0% | 4 studies (4/-) | 7.4 % | some concern | not evaluable | moderate | non important | - |
| Hypothyroidism TRAE (grade 3-4) | 2.47 [0.55, 11.04] | | < 1 | | 0% | 5 studies (5/-) | 11.9 % | some concern | serious | moderate | non important | - |
| Increase AST TRAE (grade 3-4) | 1.43 [0.43, 4.76] | | < 1 | | 0% | 3 studies (3/-) | 28.1 % | some concern | not evaluable | moderate | non important | - |
| Increased ALT TRAE (grade 3-4) | 2.98 [0.72, 12.39] | | < 1 | | 0% | 3 studies (3/-) | 6.7 % | some concern | not evaluable | moderate | non important | - |
| Increased lipase level TRAE (grade 3-4) | 11.75 [3.21, 43.03] | | < 1 | | 0% | 3 studies (3/-) | 0.0 % | some concern | not evaluable | moderate | non important | - |
| Infusion-related reactions TRAE (grade 3-4) | 1.84 [0.30, 11.19] | | < 1 | | 0% | 4 studies (4/-) | 25.6 % | some concern | not evaluable | moderate | non important | - |
| Leucopenia TRAE (grade 3-4) | 0.07 [0.01, 0.76] | | < 1 | | 81% | 4 studies (4/-) | 98.5 % | some concern | not evaluable | moderate | non important | - |
| Maculopapular rash TRAE (grade 3-4) | 3.98 [0.18, 88.64] | | < 1 | | 0% | 1 study (1/-) | 19.4 % | NA | not evaluable | | non important | - |
| Myocarditis TRAE (grade 3-4) | 1.84 [0.31, 10.77] | | < 1 | | 0% | 4 studies (4/-) | 25.0 % | some concern | not evaluable | moderate | non important | - |
| Myositis TRAE (grade 3-4) | 1.33 [0.31, 5.70] | | < 1 | | 0% | 6 studies (6/-) | 35.1 % | some concern | not evaluable | moderate | non important | - |
| Nausea TRAE (grade 3-4) | 0.47 [0.23, 0.97] | | < 1 | | 13% | 9 studies (9/-) | 98.0 % | some concern | not evaluable | moderate | non important | - |
| Nephritis TRAE (grade 3-4) | 2.30 [0.65, 8.21] | | < 1 | | 0% | 7 studies (7/-) | 10.0 % | some concern | serious | moderate | non important | - |
| Neutropenia TRAE (grade 3-4) | 0.06 [0.01, 0.24] | | < 1 | | 91% | 8 studies (8/-) | 100.0 % | some concern | serious | moderate | non important | - |
| Pancreatitis TRAE (grade 3-4) | 2.88 [0.66, 12.51] | | < 1 | | 0% | 5 studies (5/-) | 8.0 % | some concern | serious | moderate | non important | - |
| Pancytopenia TRAE (grade 3-4) | 0.11 [0.01, 0.91] | | < 1 | | 0% | 2 studies (2/-) | 97.9 % | some concern | not evaluable | moderate | non important | - |
| Peripheral neuropathy TRAE (grade 3-4) | 0.15 [0.03, 0.83] | | < 1 | | 0% | 2 studies (2/-) | 98.5 % | some concern | not evaluable | moderate | non important | - |
| Pneumonitis TRAE (grade 3-4) | 3.48 [1.20, 10.09] | | < 1 | | 0% | 7 studies (7/-) | 1.1 % | some concern | not evaluable | moderate | non important | - |
| Pruritic rash TRAE (grade 3-4) | 1.24 [0.14, 10.61] | | < 1 | | 0% | 3 studies (3/-) | 42.4 % | some concern | not evaluable | moderate | non important | - |
| Pruritus TRAE (grade 3-4) | 1.80 [0.57, 5.67] | | < 1 | | 0% | 9 studies (9/-) | 15.9 % | some concern | serious | moderate | non important | - |
| Pyrexia TRAE (grade 3-4) | 0.66 [0.14, 3.06] | | < 1 | | 0% | 3 studies (3/-) | 70.1 % | some concern | not evaluable | moderate | non important | - |
| Rash TRAE (grade 3-4) | 2.97 [1.02, 8.67] | | < 1 | | 0% | 8 studies (8/-) | 2.3 % | some concern | not evaluable | moderate | non important | - |
| Renal and urinary disorders TRAE (grade 3-4) | 8.01 [0.42, 152.12] | | < 1 | | 0% | 1 study (1/-) | 8.5 % | NA | not evaluable | | non important | - |
| Respiratory, thoracic and mediastinal disorders TRAE (grade 3-4) | 5.99 [0.30, 120.06] | | < 1 | | 0% | 1 study (1/-) | 12.4 % | NA | not evaluable | | non important | - |
| Sarcoidosis TRAE (grade 3-4) | 1.05 [0.07, 16.88] | | < 1 | | 0% | 2 studies (2/-) | 48.5 % | some concern | not evaluable | moderate | non important | - |
| Sepsis TRAE (grade 3-4) | 0.69 [0.08, 5.93] | | < 1 | | 0% | 2 studies (2/-) | 63.1 % | some concern | not evaluable | moderate | non important | - |
| Severe skin reaction TRAE (grade 3-4) | 1.36 [0.32, 5.68] | | < 1 | | 41% | 3 studies (3/-) | 33.8 % | some concern | not evaluable | moderate | non important | - |
| Stevens-Johnson syndrome TRAE (grade 3-4) | 1.36 [0.10, 17.71] | | < 1 | | 0% | 2 studies (2/-) | 40.9 % | some concern | not evaluable | moderate | non important | - |
| Stomatitis TRAE (grade 3-4) | 1.36 [0.10, 17.75] | | < 1 | | 0% | 2 studies (2/-) | 40.8 % | some concern | not evaluable | moderate | non important | - |
| Thrombocytopenia TRAE (grade 3-4) | 0.14 [0.04, 0.51] | | < 1 | | 85% | 6 studies (6/-) | 99.8 % | some concern | serious | moderate | non important | - |
| Thyroiditis TRAE (grade 3-4) | 1.26 [0.30, 5.18] | | < 1 | | 0% | 7 studies (7/-) | 37.7 % | some concern | serious | moderate | non important | - |
| Urticaria TRAE (grade 3-4) | 0.99 [0.02, 50.11] | | < 1 | | 0% | 1 study (1/-) | 50.2 % | NA | not evaluable | | non important | - |
| Uveitis TRAE (grade 3-4) | 1.00 [0.02, 50.69] | | < 1 | | 0% | 1 study (1/-) | 49.9 % | NA | not evaluable | | non important | - |
| Vitiligo TRAE (grade 3-4) | 1.00 [0.02, 50.69] | | < 1 | | 0% | 1 study (1/-) | 49.9 % | NA | not evaluable | | non important | - |
| Vomiting TRAE (grade 3-4) | 0.40 [0.12, 1.27] | | < 1 | | 45% | 4 studies (4/-) | 94.0 % | some concern | not evaluable | moderate | non important | - |
AE (grade 3-4) endpoints 00 |
| hepatitis (Autoimmune) AE (grade 3-4) | 2.01 [0.07, 60.08] | | < 1 | | 0% | 1 study (1/-) | 34.6 % | NA | not evaluable | | non important | - |
| Abdominal pain AE (grade 3-4) | 0.40 [0.10, 1.58] | | < 1 | | 0% | 1 study (1/-) | 90.3 % | NA | not evaluable | | non important | - |
| Acute kidney injury AE (grade 3-4) | 2.27 [0.58, 8.88] | | < 1 | | 0% | 1 study (1/-) | 12.0 % | NA | not evaluable | | non important | - |
| Alopecia AE (grade 3-4) | 0.16 [0.01, 3.17] | | < 1 | | 0% | 1 study (1/-) | 88.3 % | NA | not evaluable | | non important | - |
| Anaemia AE (grade 3-4) | 0.51 [0.14, 1.84] | | < 1 | | 96% | 4 studies (4/-) | 84.7 % | some concern | not evaluable | moderate | non important | - |
| Arthralgia AE (grade 3-4) | 0.78 [0.03, 18.57] | | < 1 | | 54% | 2 studies (2/-) | 56.1 % | some concern | not evaluable | moderate | non important | - |
| Asthenia AE (grade 3-4) | 0.48 [0.16, 1.41] | | < 1 | | 75% | 4 studies (4/-) | 90.9 % | some concern | not evaluable | moderate | non important | - |
| Back pain AE (grade 3-4) | 0.65 [0.22, 1.92] | | < 1 | | 0% | 2 studies (2/-) | 78.1 % | some concern | not evaluable | moderate | non important | - |
| Blood and lymphatic system disorders AE (grade 3-4) | 0.24 [0.15, 0.40] | | < 1 | | 0% | 1 study (1/-) | 100.0 % | NA | not evaluable | | non important | - |
| Blood creatinine increased AE (grade 3-4) | 1.92 [0.17, 21.35] | | < 1 | | 0% | 1 study (1/-) | 29.8 % | NA | not evaluable | | non important | - |
